tbuckley/cabot-search huggingface dataset:
Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma
Authors: Matthew Bootsma, Rana R. McKay, Hamid Emamekhoo, Rory M. Bade, Jennifer L. Schehr, Matthew C. Mannino, Anupama Singh, Serena K. Wolfe, Zachery D. Schultz, Jamie Sperger, Wanling Xie, Sabina Signoretti, Christos E. Kyriakopoulos, David Kosoff, Edwin J. Abel, Kyle T. Helzer, Nicholas Rydzewski, Hamza Bakhtiar, Yue Shi, Grace Blitzer, Michael Bassetti, John Floberg, Menggang Yu, Nan Sethakorn, Marina Sharifi, Paul M. Harari, Toni K. Choueiri, Joshua M. Lang, Shuang G. Zhao
Journal: Journal of Clinical Oncology (2022)

Liquid biopsies in metastatic renal cell carcinoma (mRCC) provide a unique approach to understand the molecular basis of treatment response and resistance. This is particularly important in the context of immunotherapies, which target key immune-tumor interactions. Unlike metastatic tissue biopsies, serial real-time profiling of mRCC is feasible with our noninvasive circulating tumor cell (CTC) approach.We collected 457 longitudinal liquid biopsies from 104 patients with mRCC enrolled in one of two studies, either a prospective cohort or a phase II multicenter adaptive immunotherapy trial. Using a novel CTC capture and automated microscopy platform, we profiled CTC enumeration and expression of HLA I and programmed cell death-ligand 1 (PD-L1). Given their diametric immunological roles, we focused on the HLA I to PD-L1 ratio (HP ratio).Patients with radiographic responses showed significantly lower CTC abundances throughout treatment. Furthermore, patients whose CTC enumeration trajectory was in the highest quartile (> 0.12 CTCs/mL annually) had shorter overall survival (median 17.0 months v 21.1 months, P < .001). Throughout treatment, the HP ratio decreased in patients receiving immunotherapy but not in patients receiving tyrosine kinase inhibitors. Patients with an HP ratio trajectory in the highest quartile (≥ 0.0012 annually) displayed significantly shorter overall survival (median 18.4 months v 21.2 months, P = .003).In the first large longitudinal CTC study in mRCC to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in mRCC.
Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells
Authors: Kunhua Qin, Peng Huang, Ruopeng Feng, Cheryl A. Keller, Scott A. Peslak, Eugene Khandros, Megan S. Saari, Xianjiang Lan, Thiyagaraj Mayuranathan, Phillip A. Doerfler, Osheiza Abdulmalik, Belinda Giardine, Stella T. Chou, Junwei Shi, Ross C. Hardison, Mitchell J. Weiss, Gerd A. Blobel
Journal: Nature Genetics (2022)
<i>Notes from the Field:</i> Self-Reported Health Symptoms Following Petroleum Contamination of a Drinking Water System — Oahu, Hawaii, November 2021–February 2022
Authors: Alyssa N. Troeschel, Ben Gerhardstein, Alex Poniatowski, Diana Felton, Amanda Smith, Krishna Surasi, Alyson M. Cavanaugh, Shanna Miko, Michele Bolduc, Vidisha Parasram, Charles Edge, Renée Funk, Maureen Orr
Journal: MMWR Morbidity and Mortality Weekly Report (2022)
Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis
Authors: Diana Buitrago-Garcia, Aziz Mert Ipekci, Leonie Heron, Hira Imeri, Lucia Araujo-Chaveron, Ingrid Arevalo-Rodriguez, Agustín Ciapponi, Muge Cevik, Anthony Hauser, Muhammad Irfanul Alam, Kaspar Meili, Eric A. Meyerowitz, Nirmala Prajapati, Xueting Qiu, Aaron Richterman, William Gildardo Robles-Rodriguez, Shabnam Thapa, Ivan Zhelyazkov, Georgia Salanti, Nicola Low
Journal: PLoS Medicine (2022)

Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic?
Effect of active vitamin D treatment on development of type 2 diabetes: DPVD randomised controlled trial in Japanese population
Authors: Tetsuya Kawahara, Gen Suzuki, Shoichi Mizuno, Tetsuya Inazu, Fumiyoshi Kasagi, Chie Kawahara, Yosuke Okada, Yoshiya Tanaka
Journal: BMJ (2022)

Abstract Objective To assess whether eldecalcitol, an active vitamin D analogue 2 , can reduce the development of type 2 diabetes among adults with impaired glucose tolerance. Design Double blinded, multicentre, randomised, placebo controlled trial. Setting Three hospitals in Japan, between June 2013 and August 2019. Participants People aged 30 years and older who had impaired glucose tolerance defined by using a 75 g oral glucose tolerance test and glycated haemoglobin level. Interventions Participants were randomised to receive active vitamin D (eldecalcitol 0.75 μg per day; n=630) or matching placebo (n=626) for three years. Main outcomes The primary endpoint was incidence of diabetes. Prespecified secondary endpoints were regression to normoglycaemia and incidence of type 2 diabetes after adjustment for confounding factors at baseline. In addition, bone densities and bone and glucose metabolism markers were assessed. Results Of the 1256 participants, 571 (45.5%) were women and 742 (59.1%) had a family history of type 2 diabetes. The mean age of participants was 61.3 years. The mean serum 25-hydroxyvitamin D concentration at baseline was 20.9 ng/mL (52.2 nmol/L); 548 (43.6%) participants had concentrations below 20 ng/mL (50 nmol/L). During a median follow-up of 2.9 years, 79 (12.5%) of 630 participants in the eldecalcitol group and 89 (14.2%) of 626 in the placebo group developed type 2 diabetes (hazard ratio 0.87, 95% confidence interval 0.67 to 1.17; P=0.39). Regression to normoglycaemia was achieved in 145 (23.0%) of 630 participants in the eldecalcitol group and 126 (20.1%) of 626 in the placebo group (hazard ratio 1.15, 0.93 to 1.41; P=0.21). After adjustment for confounding factors by multivariable fractional polynomial Cox regression analysis, eldecalcitol significantly lowered the development of diabetes (hazard ratio 0.69, 0.51 to 0.95; P=0.020). In addition, eldecalcitol showed its beneficial effect among the participants with the lower level of basal insulin secretion (hazard ratio 0.41, 0.23 to 0.71; P=0.001). During follow-up, bone mineral densities of the lumbar spine and femoral neck and serum osteocalcin concentrations significantly increased with eldecalcitol compared with placebo (all P&lt;0.001). No significant difference in serious adverse events was observed. Conclusions Although treatment with eldecalcitol did not significantly reduce the incidence of diabetes among people with pre-diabetes, the results suggested the potential for a beneficial effect of eldecalcitol on people with insufficient insulin secretion. Trial registration UMIN Clinical Trials Registry UMIN000010758.
Blood is Thicker than Water, or is It? The Possible Role of Stepparents in Pediatric Decision Making
Authors: Jaan Toelen, Ingrid Boone, Jan Van Bavel, Kris Dierickx
Journal: The American Journal of Bioethics (2022)

"Blood is Thicker than Water, or is It? The Possible Role of Stepparents in Pediatric Decision Making." The American Journal of Bioethics, 22(6), pp. 29–30
Aggregation‐Induced Emission (AIE) Photosensitizer Combined Polydopamine Nanomaterials for Organelle‐Targeting Photodynamic and Photothermal Therapy by the Recognition of Sialic Acid
Authors: Shuo Li, Yuzhi Chen, Peinan He, Yufan Ma, Yajie Cai, Xinhui Hou, Guoyang Zhang, Xin Zhang, Zhuo Wang
Journal: Advanced Healthcare Materials (2022)

Abstract The construction of organelle‐targeting nanomaterials is an effective way to improve tumor imaging and treatment. Here, a new type of composite nanomaterial named as PTTPB is developed. PTTPB is composed of organelle‐targeting aggregation‐induced emission photosensitizer TTPB and polydopamine nanomaterials. With the functional modification of TTPB, PTTPB can recognize sialic acid on the cell membrane and present mitochondrial targeted capabilities. The intake of PTTPB in cancerous cells can be increased by the recognition process of cell membrane. PTTPB can generate singlet oxygen for photodynamic therapy (PDT), and present good photothermal conversion ability with irradiation. The PTTPB with organelle‐targeting imaging‐guided can realize the tumor ablation with the synergistic effect of PDT and photothermal therapy.
Metabolomics in pulmonary medicine: extracting the most from your data
Authors: Stacey N. Reinke, Romanas Chaleckis, Craig E. Wheelock
Journal: European Respiratory Journal (2022)

<b>The metabolome enables unprecedented insight into biochemistry, providing an integrated signature of the genome, transcriptome, proteome and exposome. Measurement requires rigorous protocols combined with specialised data analysis to achieve its promise.</b>https://bit.ly/3yPiYkQ
Synthetic and Biodegradable Molybdenum(IV) Diselenide Triggers the Cascade Photo‐ and Immunotherapy of Tumor
Authors: Jiulong Zhao, Yao Zhang, Jing Zhang, Hang Wu, Jinfeng Li, Yizhou Zhao, Liying Zhang, Duowu Zou, Zhaoshen Li, Shige Wang
Journal: Advanced Healthcare Materials (2022)

In this study, a polyvinylpyrrolidone (PVP)-decorated MoSe2 (MoSe2 -PVP) nanoparticle with excellent photothermal transforming ability and chlorin E6 (Ce6) loading capacity is designed for combined tumor photothermal therapy (PTT), tumor photodynamic therapy (PDT), and immunotherapy. The light-to-heat conversion efficiency under irradiation with an 808 nm near-infrared laser is as high as 59.28%. The MoSe2 -PVP NPs could function as an artificial catalase and catalyze the decomposition of H2 O2 . Their catalytic activity and thermal durability are higher than the native catalase, which relieve the tumor hypoxia status and sensitize the tumor PDT. The data show that the synthetic MoSe2 -PVP is biodegradable, owing to the oxidation of the Mo4+ to Mo6+ . Moreover, its degradation products could increase the proportion of mature dendritic cells and CD8+ thymus (T) cells and promote the infiltration of active CD8+ T cells in tumors. The immune checkpoint inhibitor, programmed cell death protein 1 monoclonal antibody is combined with MoSe2 -PVP and it is found that its degradation product could efficiently change the immune microenvironment of the tumor.
Smart hypoxia-responsive transformable and charge-reversible nanoparticles for the deep penetration and tumor microenvironment modulation of pancreatic cancer
Authors: Hongyi Chen, Qin Guo, Yongchao Chu, Chao Li, Yiwen Zhang, Peixin Liu, Zhenhao Zhao, Yu Wang, Yifan Luo, Zheng Zhou, Tongyu Zhang, Haolin Song, Xuwen Li, Chufeng Li, Boyu Su, Haoyu You, Tao Sun, Chen Jiang
Journal: Biomaterials (2022)
Nighttime Hypertension in Chronic Kidney Disease—Are We in the Dark Without Ambulatory Blood Pressure Monitoring?
Authors: Laura Mayeda, Matthew B. Rivara
Journal: JAMA Network Open (2022)

Xiaocen Fu, MD; Hong Ren, MD; Jingyuan Xie, MD; Weiming Wang, MD; Yan Li, MD, PhD; Pingjin Gao, MD, PhD; Nan Chen, MD
Association between Vaccination with the BNT162b2 mRNA Coronavirus Disease 2019 Vaccine and Noninfectious Uveitis
Authors: Oren Tomkins-Netzer, Shaul Sar, Ofra Barnett-Griness, Binyamin Friedman, Hana Shyriaieva, Walid Saliba
Journal: Ophthalmology (2022)
Improving the Detection of ST-Segment Elevation Myocardial Infarction in Rural Settings
Authors: Uchenna R. Ofoma, Karen E. Joynt Maddox
Journal: JAMA Cardiology (2022)

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Association Between Psoriasis and Nonalcoholic Fatty Liver Disease Among Outpatient US Adults
Authors: Zhijie Ruan, Tao Lu, Yanxia Chen, Mengsi Yuan, Haoyang Yu, Ruimin Liu, Xiaoping Xie
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Recent studies have shown an association between psoriasis and nonalcoholic fatty liver disease (NAFLD) in US inpatients, but the association is still unclear in the outpatient US population. <h3>Objective</h3> To assess whether psoriasis is associated with NAFLD in outpatient US adults. <h3>Design, Setting, and Participants</h3> This population-based cross-sectional study used data on US adults aged 20 to 59 years from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014 cycles. Data were analyzed from June to September 2021. <h3>Exposures</h3> Self-reported psoriasis. <h3>Main Outcomes and Measures</h3> The main outcome was NAFLD, defined as a US fatty liver index score greater than 30. Sampling weights were calculated according to NHANES guidelines. <h3>Results</h3> Among 5672 adults included in this study (mean age, 38.9 years [95% CI, 38.4-39.3 years]; 2999 [51.1%] female), 148 (3.0%) had psoriasis and 5524 (97.0%) did not have psoriasis. A total of 1558 participants (26.8%) were classified as having NAFLD. Compared with participants without psoriasis, those with psoriasis had a higher prevalence of NAFLD (32.7% [52] vs 26.6% [1506]). In a multivariable logistic regression model adjusted for age, sex, race and ethnicity, educational level, family income, marital status, NHANES cycles, diabetes, metabolic syndrome, and smoking and alcohol drinking status, psoriasis was associated with NAFLD (odds ratio [OR], 1.67; 95% CI, 1.03-2.70). In subgroup analyses, psoriasis was associated with NAFLD among men (OR, 2.16; 95% CI, 1.10-4.24), among those aged 20 to 39 years (OR, 2.48; 95% CI, 1.09-5.67), and among those without diabetes (1.70; 95% CI, 1.05-2.76). An association between psoriasis and NAFLD was found in sensitivity analyses that excluded potential hepatotoxic medication use (OR, 1.72; 95% CI, 1.01-2.95) or non-Hispanic Black participants (OR, 1.76; 95% CI, 1.07-2.87), redefined NAFLD based on the hepatic steatosis index score (OR, 1.59; 95% CI, 1.01-2.50), and used inverse probability of treatment weighting (OR, 1.43; 95% CI, 1.09-1.86). <h3>Conclusions and Relevance</h3> In this cross-sectional study, psoriasis was associated with NAFLD in the outpatient US adult population in adjusted models. This association may be important to consider in the context of clinicians prescribing potentially hepatotoxic medication for psoriasis management.
ezQTL: A Web Platform for Interactive Visualization and Colocalization of QTLs and GWAS Loci
Authors: Tongwu Zhang, Alyssa Klein, Jian Sang, Jiyeon Choi, Kevin M. Brown
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Genome-wide association studies (GWAS) have identified thousands of genomic loci associated with complex diseases and traits, including cancer. The vast majority of common trait-associated variants identified via GWAS fall in non-coding regions of the genome, posing a challenge in elucidating the causal variants, genes, and mechanisms involved. Expression quantitative trait locus (eQTL) and other molecular QTL studies have been valuable resources in identifying candidate causal genes from GWAS loci through statistical colocalization methods. While QTL colocalization is becoming a standard analysis in post-GWAS investigation, an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been lacking. Here, we present ezQTL, a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium (LD) patterns (1000 Genomes Project, UK Biobank, or user-provided data). This application allows users to perform data quality control for variants matched between different datasets, LD visualization, and two-trait colocalization analyses using two state-of-the-art methodologies (eCAVIAR and HyPrColoc), including batch processing. ezQTL is a free and publicly available cross-platform web tool, which can be accessed online at https://analysistools.cancer.gov/ezqtl.
Evaluation of Antipsychotic Reduction Efforts in Patients With Dementia in Veterans Health Administration Nursing Homes
Authors: Lauren B. Gerlach, Donovan T. Maust, Helen C. Kales, Myron Chang, H. Myra Kim, Ilse R. Wiechers, Kara Zivin
Journal: American Journal of Psychiatry (2022)

Objective: The Veterans Health Administration (VHA) and the Centers for Medicare and Medicaid Services (CMS) each created initiatives to reduce off-label use of antipsychotics in patients with dementia in nursing homes. Although CMS has reported antipsychotic reductions, the impact on prescribing of antipsychotic and other CNS-active medications in the VHA remains unclear. The authors evaluated national trends in antipsychotic and other CNS-active medication prescribing for nursing home patients with dementia in the VHA. Methods: The study sample was all veterans with dementia residing in VHA nursing homes for more than 30 days (N=35,742). Using an interrupted time-series design, the quarterly prevalences of antipsychotic, antidepressant, antiepileptic, anxiolytic, opioid, and memory medication prescribing were evaluated from FY2009 through FY2018. Results: Antipsychotic prescribing in VHA nursing homes declined from FY2009 to FY2018 (from 33.7% to 27.5%), with similar declines in anxiolytic prescribing (from 33.5% to 27.1%). During this period, prescribing of antiepileptics, antidepressants, and opioids increased significantly (antiepileptics: from 26.8% to 43.3%; antidepressants: from 56.8% to 63.4%; opioids: from 32.6% to 41.2%). Gabapentin served as the main driver of antiepileptic increases (from 11.1% to 23.5%). Increases in antidepressant prescribing included sertraline, mirtazapine, and trazodone. From FY2009 to FY2018, the overall prescribing of non-antipsychotic psychotropic medications grew from 75.0% to 81.1%. Conclusions: Antipsychotic and anxiolytic prescribing for VHA nursing home residents with dementia declined, although overall prescribing of other psychotropic and opioid medications increased. Policies focused primarily on reducing antipsychotic use without considering use in the context of other medications may contribute to growth in alternative medication classes with even less evidence of benefit and similar risks.
Cytotoxic innate lymphoid cells sense cancer cell-expressed interleukin-15 to suppress human and murine malignancies
Authors: Emily R. Kansler, Saïda Dadi, Chirag Krishna, Briana G. Nixon, Efstathios G. Stamatiades, Ming Liu, Fengshen Kuo, Jing Zhang, Xian Zhang, Kristelle Capistrano, Kyle A. Blum, Kate Weiss, Ross M. Kedl, Guangwei Cui, Koichi Ikuta, Timothy A. Chan, Christina S. Leslie, A. Ari Hakimi, Ming O. Li
Journal: Nature Immunology (2022)
<i>QuickStats: </i>Percentage Distribution of Deaths Involving Injuries from Recreational and Nonrecreational Use of Watercraft,* by Month — United States, 2018–2020
Authors: R Spencer
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Deaths were identified using International Classification of Diseases, Tenth Revision underlying cause of death codes V90-V94 (water transport) for a total of 1,508 deaths during 2018-2020.Water transport includes recreational and nonrecreational use of motorized (e.g., merchant ship, ferry,
Perioperative arginine prevents metastases by accelerating natural killer cell recovery after surgery
Authors: Leonard Angka, Christiano Tanese de Souza, Katherine E. Baxter, Sarwat T. Khan, Marisa Market, Andre B. Martel, Lee-Hwa Tai, Michael A. Kennedy, John C. Bell, Rebecca C. Auer
Journal: Molecular Therapy (2022)

Profound natural killer (NK) cell suppression after cancer surgery is a main driver of metastases and recurrence, for which there is no clinically approved intervention available. Surgical stress is known to cause systemic postoperative changes that negatively modulate NK cell function including the expansion of surgery-induced myeloid-derived suppressor cells (Sx-MDSCs) and a marked reduction in arginine bioavailability. In this study, we determine that Sx-MDSCs regulate systemic arginine levels in the postoperative period and that restoring arginine imbalance after surgery by dietary intake alone was sufficient to significantly reduce surgery-induced metastases in our preclinical murine models. Importantly, the effects of perioperative arginine were dependent upon NK cells. Although perioperative arginine did not prevent immediate NK cell immunoparalysis after surgery, it did accelerate their return to preoperative cytotoxicity, interferon gamma secretion, and activating receptor expression. Finally, in a cohort of patients with colorectal cancer, postoperative arginine levels were shown to correlate with their Sx-MDSC levels. Therefore, this study lends further support for the use of perioperative arginine supplementation by improving NK cell recovery after surgery.